Porokeratotic eccrine ostial and dermal duct nevus or porokeratotic eccrine nevus (PEN) is a rare nevoid condition characterized by asymptomatic spiny, keratotic papules, and plaques in linear distribution along Blaschko's lines on the extremities clinically and discrete vertical cornoid lamellae at eccrine ostia pathologically. Keratitis–ichthyosis–deafness (KID) syndrome manifests generalized erythematous plaques with tiny papules and keratotic spicules. Both rare diseases are associated with mutations of the GJB2 gene encoding for gap junction protein, connexin 26. We present a case of KID syndrome in an 11-year-old boy. The patient presented with bilateral hearing loss, and large erythematous plaques with grained leather-like appearance and occasional keratotic spicules on the face and trunk as well as prominent hyperkeratosis on the acral parts, especially distal digits. Skin biopsy of two skin lesions revealed features of PEN. Mutation analysis of peripheral blood revealed GJB2 c. 263C>T (p.A88V). This is the first report of GJB2 gene mutation in a Taiwanese boy with KID syndrome. The histologic features of PEN in the present case provide additional support that PEN may be part of the manifestation of KID syndrome.

An 11-year-old Taiwanese boy presented with generalized, large erythematous plaques on the face, scalp, trunk and limbs, and diffuse palmoplantar hyperkeratosis that worsened progressively since birth [Figure 1]. The plaques had a fine granular surface with uniform, tiny papules, many of which were surmounted by keratin spicules [Figure 2]a and [Figure 2]b. In addition, bilateral sensorineural hearing impairment had been discovered since infancy, but an ophthalmologic evaluation showed a negative finding. Histopathology revealed characteristic features of PEN [Figure 2]c. The patient did not have obvious hypohidrosis or increased susceptibility to infection. Other clinical manifestations include teeth in disarray, partial nonscarring hair loss, onycholysis affecting the fingers, and nail dystrophy of toes. There was no similar clinical manifestation in his parents or siblings.

Figure 1: Large plaques of erythrokeratoderma are present on the scalp, face, lips, and trunk, and marked palmoplantar hyperkeratosis with periungual involvement

Genomic DNA was extracted from the whole blood samples of the patient and his mother with informed consent. The coding region of exon 2 of the GJB2 gene on chromosome 13q12.11 was amplified by the polymerase chain reaction and sequenced. Results revealed that the child was heterozygous for single nucleotide substitution at residue position 263 of the GJB2 domain segment (GCG to GTG, substitution of alanine for valine at position 88), c. 263C >T (p.A88V) [Figure 2]d.

Discussion

Mutations in GJB2, the gene encoding Cx26, have been detected in multiple congenital skin disorders including KID syndrome and PEN.[2] Four different point mutations of GJB2 (Cx26, p.G12R, p.N14Y, p.G45E, and p.M93I) have been reported in PEN, Cx26 p.G12R was identified in a patient with KID syndrome with additional features of PEN,[3] the remaining three mutations were detected in patients with pure PEN.[1],[4] Of these four mutations, the first three have been previously documented in KID syndrome. In addition to some overlapping features between KID syndrome and PEN, Easton et al.[1] also observed two mothers with PEN giving birth to children with KID syndrome. These observations suggest that KID syndrome may be a generalized form of PEN.

Titeux et al.[5] reported a case where the mother with linear skin lesions gave birth to a baby with severe KID syndrome. Cutaneous mosaicism of Cx26 (p. Asp50Asn) was detected in the baby's blood, but not in the mother's blood. However, the same mutation was identified in a linear lesion from the mother. This case was reported as the first example of KID syndrome inheritance from a proven mosaic mother who displayed lesions consistent with Type 1 segmental manifestation. In the study of two cases with generalized PEN by Easton et al.,[1]GJB2 mutations (Cx26 p.N14Y and p.M93I) were found only in the affected skin, and not in the normal skin or peripheral blood. The authors conclude that PEN may be caused by mosaic GJB2 mutation.[1] Levinsohn et al.[4] further proved that somatic GJB2 mutation is sufficient to cause PEN by whole-exome sequencing in a patient with widespread PEN and detected p.G45E mutation only in the skin lesion, not in the blood.

Blaschko lines represent the developmental path of ectodermal precursor cells, and postzygotic somatic mutations in the precursor cells can lead to linear band of abnormal keratinocytes.[2] As early somatic mutation can affect multiple embryonic lineages, individuals with somatic mosaicism are capable of transmitting the systemic disease to their offspring. Hence, patients with PEN should be counseled regarding the risk of having a child with KID syndrome.[4]

In KID syndrome, cutaneous lesions and hearing loss generally present in the early childhood while ocular symptoms appear later in KID syndrome.[6] Two cases of Cx26 p.A88V heterozygous mutation have been previously reported in KID syndrome, both patients had chronic infection leading to the lethal outcome.[7],[8] The actual mechanism for the chronic infection was unknown but might involve immunodeficiency. Our patient manifested large plaques studded with numerous uniform, tiny papules, corresponding to the hypertrophic acrosyringia associated central keratotic spicules as a manifestation of vertical cornoid lamellae, features typical of PEN but lacking blaschkoid pattern. The clinicopathologic findings in our case provide additional support that PEN may be part of the manifestation of KID syndrome.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.